Advertisement

NLRP3 inflammasome in neurodegenerative disease

Published:August 08, 2022DOI:https://doi.org/10.1016/j.trsl.2022.08.006

      Abstract

      Neurodegenerative diseases are characterized by a dysregulated neuro-glial microenvironment, culminating in functional deficits resulting from neuronal cell death. Inflammation is a hallmark of the neurodegenerative microenvironment and despite a critical role in tissue homeostasis, increasing evidence suggests that chronic inflammatory insult can contribute to progressive neuronal loss. Inflammation has been studied in the context of neurodegenerative disorders for decades but few anti-inflammatory treatments have advanced to clinical use. This is likely due to the related challenges of predicting and mitigating off-target effects impacting the normal immune response while detecting inflammatory signatures that are specific to the progression of neurological disorders. Inflammasomes are pro-inflammatory cytosolic pattern recognition receptors functioning in the innate immune system. Compelling pre-clinical data has prompted an intense interest in the role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in neurodegenerative disease. NLRP3 is typically inactive but can respond to sterile triggers commonly associated with neurodegenerative disorders including protein misfolding and aggregation, mitochondrial and oxidative stress, and exposure to disease-associated environmental toxicants. Clear evidence of enhanced NLRP3 inflammasome activity in common neurodegenerative diseases has coincided with rapid advancement of novel small molecule therapeutics making the NLRP3 inflammasome an attractive target for near-term interventional studies. In this review, we highlight evidence from model systems and patients indicating inflammasome activity in neurodegenerative disease associated with the NLRP3 inflammasome's ability to recognize pathologic forms of amyloid-β, tau, and α-synuclein. We discuss inflammasome-driven pyroptotic processes highlighting the potential utility of evaluating extracellular inflammasome-related proteins in the context of biomarker discovery. We complete the report by pointing out gaps in our understanding of intracellular modifiers of inflammasome activity and mechanisms regulating the resolution of inflammasome activation. The literature review and perspectives provide a conceptual platform for continued analysis of inflammation in neurodegenerative diseases through the study of inflammasomes and pyroptosis, mechanisms of inflammation and cell death now recognized to function in multiple highly prevalent neurological disorders.

      Abbreviations:

      ALRs (absent in melanoma 2-like receptors), α-syn (alpha-synuclein), AD (Alzheimer's disease), (amyloid beta), APP (amyloid precursor protein), ALS (amyotrophic lateral sclerosis), ASC (apoptosis-associated speck-like protein containing a CARD)), BBB (blood brain barrier), BMDMs (bone-marrow derived macrophages), CARD (caspase activation and recruitment domain), CNS (Central nervous system), CSF (cerebrospinal fluid), COPD (chronic obstructive pulmonary disease), CRID (cytokine release inhibitory drug), DAMPs (danger associated molecular patterns), DPI (diphenyliodonium), DA (dopaminergic), Drd2 (dopamine D2 receptor), ESCRT (endosomal sorting complexes required for transport), EAE (experimental autoimmune encephalomyelitis), EVs (extracellular vesicles), GSDMD (Gasdermin D), hIPSCs (human induced pluripotent stem cells), HIV-1 (human immunodeficiency virus), HLA (human leukocyte antigen), IKK (IκB kinase), IFN-β (interferon-β), LPS (lipopolysaccharide), MCI (mild cognitive impairment), MS (Multiple Sclerosis), MVBs (multivesicular bodies), NLRP3 (NLR family pyrin domain containing 3), NLRs (nucleotide-binding domain-like receptors), PD (Parkinson's disease), PAMPs (pathogen associated molecular patterns), PET (positron emission tomography), PK (pharmacokinetics), PTMs (post-translational modifications), PSEN1/PS1 (presenilin 1), PSEN2/PS2 (presenilin 2), ROS (Reactive oxygen species), RvD2 (Resolvin D2), SOD1 (superoxide dismutase 1), SNpC (substantia nigra pars compacta), TDP-43 (TAR DNA binding protein 43), TBI (traumatic brain injury), TLR (toll-like receptor), TCA (tricarboxylic acid)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Mao M.
        • et al.
        Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning.
        Proc Natl Acad Sci U S A,. 1998; 95: 8175-8180
        • Cuisset L.
        • et al.
        Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44.
        Am J Hum Genet. 1999; 65: 1054-1059
        • Hoffman H.M.
        • et al.
        Identification of a locus on chromosome 1q44 for familial cold urticaria.
        Am J Hum Genet. 2000; 66: 1693-1698
        • Hoffman H.M.
        • et al.
        Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome.
        Nat Genet. 2001; 29: 301-305
        • Latz E.
        • Xiao T.S.
        • Stutz A.
        Activation and regulation of the inflammasomes.
        Nat Rev Immunol. 2013; 13: 397-411
        • He Y.
        • Hara H.
        • Nunez G.
        Mechanism and regulation of NLRP3 inflammasome activation.
        Trends Biochem Sci. 2016; 41: 1012-1021
        • Broz P.
        • Dixit V.M.
        Inflammasomes: mechanism of assembly, regulation and signalling.
        Nat Rev Immunol. 2016; 16: 407-420
        • Zheng M.
        • Kanneganti T.D.
        The regulation of the ZBP1-NLRP3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (PANoptosis).
        Immunol Rev. 2020; 297: 26-38
        • Strowig T.
        • et al.
        Inflammasomes in health and disease.
        Nature. 2012; 481: 278-286
        • Schroder K.
        • Tschopp J.
        The inflammasomes.
        Cell. 2010; 140: 821-832
        • Mariathasan S.
        • et al.
        Cryopyrin activates the inflammasome in response to toxins and ATP.
        Nature. 2006; 440: 228-232
        • Pan P.
        • et al.
        SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation.
        Nat Commun. 2021; 12: 4664
        • Tschopp J.
        • Schroder K.
        NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production?.
        Nat Rev Immunol. 2010; 10: 210-215
        • Bauernfeind F.G.
        • et al.
        Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression.
        J Immunol. 2009; 183: 787-791
        • He Y.
        • et al.
        NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux.
        Nature. 2016; 530: 354-357
        • Fink S.L.
        • Cookson B.T.
        Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells.
        Infect Immun. 2005; 73: 1907-1916
        • Broz P.
        • Pelegrin P.
        • Shao F.
        The gasdermins, a protein family executing cell death and inflammation.
        Nat Rev Immunol. 2020; 20: 143-157
        • Patel M.N.
        • et al.
        Inflammasome Priming in Sterile Inflammatory Disease.
        Trends Mol Med. 2017; 23: 165-180
        • Murphy M.P.
        How mitochondria produce reactive oxygen species.
        Biochem J. 2009; 417: 1-13
        • Zhou R.
        • et al.
        A role for mitochondria in NLRP3 inflammasome activation.
        Nature. 2011; 469: 221-226
        • Bauernfeind F.
        • et al.
        Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome.
        J Immunol. 2011; 187: 613-617
        • Folco E.J.
        • et al.
        Moderate hypoxia potentiates interleukin-1beta production in activated human macrophages.
        Circ Res. 2014; 115: 875-883
        • Panchanathan R.
        • Liu H.
        • Choubey D.
        Hypoxia primes human normal prostate epithelial cells and cancer cell lines for the NLRP3 and AIM2 inflammasome activation.
        Oncotarget. 2016; 7: 28183-28194
        • Lampropoulou V.
        • et al.
        Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation.
        Cell Metab. 2016; 24: 158-166
        • Moon J.S.
        • et al.
        UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during sepsis.
        J Clin Invest. 2015; 125: 665-680
        • Xiao H.
        • et al.
        Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility.
        Circulation. 2013; 128: 632-642
        • Suresh R.
        • et al.
        Complement-mediated 'bystander' damage initiates host NLRP3 inflammasome activation.
        J Cell Sci. 2016; 129: 1928-1939
        • Won J.H.
        • et al.
        Rotenone-induced impairment of mitochondrial electron transport chain confers a selective priming signal for NLRP3 inflammasome activation.
        J Biol Chem. 2015; 290: 27425-27437
        • Anderson F.L.
        • et al.
        Inflammasomes: An Emerging Mechanism Translating Environmental Toxicant Exposure Into Neuroinflammation in Parkinson's Disease.
        Toxicol Sci. 2018; 166: 3-15
        • Latz E.
        • Duewell P.
        NLRP3 inflammasome activation in inflammaging.
        Semin Immunol. 2018; 40: 61-73
        • Cicolari S.
        • Catapano A.L.
        • Magni P.
        Inflammaging and neurodegenerative diseases: role of NLRP3 inflammasome activation in brain atherosclerotic vascular disease.
        Mech Ageing Dev. 2021; 195111467
        • Luciunaite A.
        • et al.
        Soluble Abeta oligomers and protofibrils induce NLRP3 inflammasome activation in microglia.
        J Neurochem. 2019; : e14945
        • Scheiblich H.
        • et al.
        Microglial NLRP3 Inflammasome Activation upon TLR2 and TLR5 ligation by distinct α-synuclein assemblies.
        The J Immunol. 2021; 207: 2143-2154
        • Amores-Iniesta J.
        • et al.
        Extracellular ATP activates the NLRP3 inflammasome and is an early danger signal of skin allograft rejection.
        Cell Rep. 2017; 21: 3414-3426
        • Sadatomi D.
        • et al.
        Mitochondrial function is required for extracellular ATP-induced NLRP3 inflammasome activation.
        J Biochem. 2017; 161: 503-512
        • Halle A.
        • et al.
        The NALP3 inflammasome is involved in the innate immune response to amyloid-beta.
        Nat Immunol. 2008; 9: 857-865
        • Nomura J.
        • et al.
        Intracellular ATP Decrease Mediates NLRP3 Inflammasome Activation upon Nigericin and Crystal Stimulation.
        J Immunol. 2015; 195: 5718-5724
        • Billingham L.K.
        • et al.
        Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation.
        Nat Immunol. 2022; 23: 692-704
      1. 2020 Alzheimer's disease facts and figures. Alzheimers Dement, 2020.

        • Norton S.
        • et al.
        Potential for primary prevention of Alzheimer's disease: an analysis of population-based data.
        Lancet Neurol. 2014; 13: 788-794
        • Donev R.
        • et al.
        Neuronal death in Alzheimer's disease and therapeutic opportunities.
        J Cell Mol Med. 2009; 13: 4329-4348
        • Bloom G.S.
        Amyloid-beta and tau: the trigger and bullet in Alzheimer disease pathogenesis.
        JAMA Neurol. 2014; 71: 505-508
        • Goate A.
        • et al.
        Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.
        Nature. 1991; 349: 704-706
        • Selkoe D.J.
        • Hardy J.
        The amyloid hypothesis of Alzheimer's disease at 25 years.
        EMBO Mol Med. 2016; 8: 595-608
        • De Strooper B.
        • Karran E.
        The cellular phase of Alzheimer's disease.
        Cell. 2016; 164: 603-615
        • Heneka M.T.
        • et al.
        NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice.
        Nature. 2013; 493: 674-678
        • Ising C.
        • et al.
        NLRP3 inflammasome activation drives tau pathology.
        Nature. 2019; 575: 669-673
        • Venegas C.
        • et al.
        Microglia-derived ASC specks cross-seed amyloid-beta in Alzheimer's disease.
        Nature. 2017; 552: 355-361
        • Friker L.L.
        • et al.
        beta-amyloid clustering around ASC fibrils boosts its toxicity in microglia.
        Cell Rep. 2020; 30 (e6): 3743-3754
        • Götz J.
        • Halliday G.
        • Nisbet R.M.
        Molecular pathogenesis of the tauopathies.
        Ann Rev Pathol: Mechan Dis. 2019; 14: 239-261
        • Stancu I.C.
        • et al.
        Aggregated Tau activates NLRP3-ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo.
        Acta Neuropathol. 2019; 137: 599-617
        • Jiang S.
        • et al.
        Proteopathic tau primes and activates interleukin-1β via myeloid-cell-specific MyD88- and NLRP3-ASC-inflammasome pathway.
        Cell Rep. 2021; 36109720
        • Liu Y.
        • et al.
        Beta-amyloid activates NLRP3 inflammasome via TLR4 in mouse microglia.
        Neurosci Lett. 2020; 736135279
        • Islam J.
        • et al.
        GPCR19 regulates P2×7R-mediated NLRP3 inflammasomal activation of microglia by amyloid β in a mouse model of alzheimer's disease.
        Front Immunol. 2022; 13766919
        • Bibič L.
        • Stokes L.
        Revisiting the Idea That Amyloid-β Peptide Acts as an Agonist for P2×7.
        Front Mol Neurosci. 2020; 13
        • Sbai O.
        • et al.
        AGE-TXNIP axis drives inflammation in Alzheimer's by targeting Aβ to mitochondria in microglia.
        Cell Death Dis. 2022; 13: 302
        • Okada M.
        • et al.
        The Lysosome Rupture-activated TAK1-JNK Pathway Regulates NLRP3 Inflammasome Activation*.
        J Biol Chem. 2014; 289: 32926-32936
        • Flavin W.P.
        • et al.
        Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins.
        Acta Neuropathol. 2017; 134: 629-653
        • Han C.
        • et al.
        New mechanism of nerve injury in Alzheimer's disease: beta-amyloid-induced neuronal pyroptosis.
        J Cell Mol Med. 2020; 24: 8078-8090
        • Zhao N.
        • et al.
        Amentoflavone suppresses amyloid beta1-42 neurotoxicity in Alzheimer's disease through the inhibition of pyroptosis.
        Life Sci. 2019; 239117043
        • Gustin A.
        • et al.
        NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes.
        PLoS One. 2015; 10e0130624
        • Couturier J.
        • et al.
        Activation of phagocytic activity in astrocytes by reduced expression of the inflammasome component ASC and its implication in a mouse model of Alzheimer disease.
        J Neuroinflammation. 2016; 13: 20
        • Freeman L.
        • et al.
        NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes.
        J Exp Med. 2017; 214: 1351-1370
        • Ebrahimi T.
        • et al.
        alpha1-antitrypsin mitigates NLRP3-inflammasome activation in amyloid beta1-42-stimulated murine astrocytes.
        J Neuroinflammation. 2018; 15: 282
        • Wilson E.H.
        • Weninger W.
        • Hunter C.A.
        Trafficking of immune cells in the central nervous system.
        J Clin Invest. 2010; 120: 1368-1379
        • Rezai-Zadeh K.
        • Gate D.
        • Town T.
        CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?.
        J Neuroimmune Pharmacol. 2009; 4: 462-475
        • Saresella M.
        • et al.
        The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer's disease.
        Mol neurodegeneration. 2016; 11 (23-23)
        • Marras C.
        • et al.
        Prevalence of Parkinson's disease across North America.
        NPJ Parkinsons Dis. 2018; 4: 21
        • Eriksen J.L.
        • Wszolek Z.
        • Petrucelli L.
        Molecular pathogenesis of Parkinson disease.
        Arch Neurol. 2005; 62: 353-357
        • Rodriguez-Oroz M.C.
        • et al.
        Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms.
        Lancet Neurol. 2009; 8: 1128-1139
        • Postuma R.B.
        • et al.
        Identifying prodromal Parkinson's disease: pre-motor disorders in Parkinson's disease.
        Mov Disord. 2012; 27: 617-626
        • Spillantini M.G.
        • et al.
        alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies.
        Proc Natl Acad Sci U S A,. 1998; 95: 6469-6473
        • Cheng H.C.
        • Ulane C.M.
        • Burke R.E.
        Clinical progression in Parkinson disease and the neurobiology of axons.
        Ann Neurol. 2010; 67: 715-725
        • Fearnley J.M.
        • Lees A.J.
        Ageing and Parkinson's disease: substantia nigra regional selectivity.
        Brain. 1991; 114: 2283-2301
        • Polymeropoulos M.H.
        • et al.
        Mapping of a gene for Parkinson's disease to chromosome 4q21-q23.
        Science. 1996; 274: 1197-1199
        • Chartier-Harlin M.C.
        • et al.
        Alpha-synuclein locus duplication as a cause of familial Parkinson's disease.
        Lancet. 2004; 364: 1167-1169
        • Singleton A.B.
        • et al.
        alpha-Synuclein locus triplication causes Parkinson's disease.
        Science. 2003; 302: 841
        • Luk K.C.
        • et al.
        Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice.
        Science. 2012; 338: 949-953
        • Wang Q.
        • Liu Y.
        • Zhou J.
        Neuroinflammation in Parkinson's disease and its potential as therapeutic target.
        Transl Neurodegener. 2015; 4: 19
        • McGeer P.L.
        • et al.
        Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains.
        Neurology. 1988; 38: 1285-1291
        • Chen H.
        • et al.
        Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease.
        Arch Neurol. 2003; 60: 1059-1064
        • Gao X.
        • et al.
        Use of ibuprofen and risk of Parkinson disease.
        Neurology. 2011; 76: 863-869
        • Hamza T.H.
        • et al.
        Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.
        Nat Genet. 2010; 42: 781-785
        • International Parkinson Disease Genomics C.
        • et al.
        Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies.
        Lancet. 2011; 377: 641-649
        • Hollenbach J.A.
        • et al.
        A specific amino acid motif of HLA-DRB1 mediates risk and interacts with smoking history in Parkinson's disease.
        Proc Natl Acad Sci U S A,. 2019; 116: 7419-7424
        • Wang W.
        • et al.
        Caspase-1 causes truncation and aggregation of the Parkinson's disease-associated protein alpha-synuclein.
        Proc Natl Acad Sci U S A,. 2016; 113: 9587-9592
        • Anderson F.L.
        • et al.
        Plasma-borne indicators of inflammasome activity in Parkinson's disease patients.
        NPJ Parkinsons Dis. 2021; 7: 2
        • Gordon R.
        • et al.
        Inflammasome inhibition prevents alpha-synuclein pathology and dopaminergic neurodegeneration in mice.
        Sci Transl Med. 2018; 10: 465
        • von Herrmann K.M.
        • et al.
        NLRP3 expression in mesencephalic neurons and characterization of a rare NLRP3 polymorphism associated with decreased risk of Parkinson's disease.
        NPJ Parkinsons Dis. 2018; 4: 24
        • Panicker N.
        • et al.
        Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson's disease.
        Neuron. 2022; : 2422-2437
        • Langston J.W.
        The MPTP Story.
        J Parkinsons Dis. 2017; 7: S11-S19
        • Langston J.W.
        • et al.
        Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey.
        Brain Res. 1984; 292: 390-394
        • Lee E.
        • et al.
        MPTP-driven NLRP3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration.
        Cell Death Differ. 2019; 26: 213-228
        • Qiao C.
        • et al.
        Caspase-1 deficiency alleviates dopaminergic neuronal death via inhibiting caspase-7/AIF Pathway in MPTP/p mouse model of Parkinson's disease.
        Mol Neurobiol. 2017; 54: 4292-4302
        • Qiao C.
        • et al.
        Inhibition of the hepatic Nlrp3 protects dopaminergic neurons via attenuating systemic inflammation in a MPTP/p mouse model of Parkinson's disease.
        J Neuroinflammation. 2018; 15: 193
        • Zhang X.
        • et al.
        Salidroside ameliorates Parkinson's disease by inhibiting NLRP3-dependent pyroptosis.
        Aging (Albany NY). 2020; 12: 9405-9426
        • von Herrmann K.M.
        • et al.
        Slc6a3-dependent expression of a CAPS-associated Nlrp3 allele results in progressive behavioral abnormalities and neuroinflammation in aging mice.
        J Neuroinflammation. 2020; 17: 213
        • Zhu J.
        • et al.
        Dopamine D2 receptor restricts astrocytic NLRP3 inflammasome activation via enhancing the interaction of beta-arrestin2 and NLRP3.
        Cell Death Differ. 2018; 25: 2037-2049
      2. Codolo, G., et al., Triggering of inflammasome by aggregated a – synuclein, an inflammatory response in synucleinopathies. 2013; 8(1): e55375.

        • Panicker N.
        • et al.
        Fyn kinase regulates misfolded α-synuclein uptake and NLRP3 inflammasome activation in microglia.
        J Exp Med. 2019; 216: 1411-1430
        • Pike A.F.
        • et al.
        α-Synuclein evokes NLRP3 inflammasome-mediated IL-1β secretion from primary human microglia.
        Glia. 2021; 69: 1413-1428
        • Trudler D.
        • et al.
        Soluble α-synuclein–antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia.
        Proc Nationl Acad Sci. 2021; 118e2025847118
        • Fink A.L.
        The Aggregation and Fibrillation of α-Synuclein.
        Acc Chem Res. 2006; 39: 628-634
        • Mehra S.
        • Sahay S.
        • Maji S.K.
        α-Synuclein misfolding and aggregation: Implications in Parkinson's disease pathogenesis.
        Biochim Biophys Acta Proteins Proteom. 2019; 1867: 890-908
        • Teplow D.B.
        On the subject of rigor in the study of amyloid β-protein assembly.
        Alzheimer's Res Ther. 2013; 5: 39
        • Earls R.H.
        • et al.
        Intrastriatal injection of preformed alpha-synuclein fibrils alters central and peripheral immune cell profiles in non-transgenic mice.
        Journal of Neuroinflammation. 2019; 16: 250
        • Duffy M.F.
        • et al.
        Lewy body-like alpha-synuclein inclusions trigger reactive microgliosis prior to nigral degeneration.
        J Neuroinflam. 2018; 15: 129
        • Buell A.K.
        • et al.
        Solution conditions determine the relative importance of nucleation and growth processes in α-synuclein aggregation.
        Proc Nationl Acad Sci. 2014; 111: 7671-7676
        • Lövestam S.
        • et al.
        Assembly of recombinant tau into filaments identical to those of Alzheimer's disease and chronic traumatic encephalopathy.
        Elife. 2022; 11
        • Fujiwara S.
        • et al.
        Dynamic properties of human α-synuclein related to propensity to amyloid fibril formation.
        J Mol Biol. 2019; 431: 3229-3245
        • Stoll A.C.
        • Sortwell C.E.
        Leveraging the preformed fibril model to distinguish between alpha-synuclein inclusion- and nigrostriatal degeneration-associated immunogenicity.
        Neurobiol Dis. 2022; 171105804
        • Deleidi M.
        • Isacson O.
        Viral and inflammatory triggers of neurodegenerative diseases.
        Sci Transl Med. 2012; 4 (ps3): 121
        • Albornoz E.
        SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike-ACE2 receptor interaction.
        bioRxiv. 2022; : 138-160
        • Cohen M.E.
        • et al.
        A case of probable Parkinson's disease after SARS-CoV-2 infection.
        Lancet Neurol. 2020; 19: 804-805
        • Mendez-Guerrero A.
        • et al.
        Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection.
        Neurology. 2020; 95: e2109-e2118
        • Faber I.
        • et al.
        Coronavirus disease 2019 and Parkinsonism: a non-post-encephalitic case.
        Mov Disord. 2020; 35: 1721-1722
        • Fan Z.
        • et al.
        Systemic activation of NLRP3 inflammasome and plasma alpha-synuclein levels are correlated with motor severity and progression in Parkinson's disease.
        J Neuroinflammation. 2020; 17: 11
        • Hardiman O.
        • et al.
        Amyotrophic lateral sclerosis.
        Nature Rev Dis Primers. 2017; 3: 17071
        • Masrori P.
        • Van Damme P.
        Amyotrophic lateral sclerosis: a clinical review.
        Eur J Neurol. 2020; 27: 1918-1929
        • Neumann M.
        • et al.
        Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.
        Science. 2006; 314: 130-133
        • Turner M.R.
        • et al.
        Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study.
        Neurobiol Dis. 2004; 15: 601-609
        • Van Schoor E.
        • et al.
        Increased pyroptosis activation in white matter microglia is associated with neuronal loss in ALS motor cortex.
        Acta Neuropathol. 2022; : 393-411
        • Banerjee P.
        • et al.
        NLRP3 inflammasome as a key molecular target underlying cognitive resilience in amyotrophic lateral sclerosis.
        The J Pathol. 2022; 256: 262-268
        • Gurney M.E.
        • et al.
        Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation.
        Science. 1994; 264: 1772-1775
        • Deora V.
        • et al.
        The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins.
        Glia. 2020; 68: 407-421
        • Gugliandolo A.
        • et al.
        NLRP3 inflammasome activation in a transgenic amyotrophic lateral sclerosis model.
        Inflammation. 2018; 41: 93-103
        • Meissner F.
        • Molawi K.
        • Zychlinsky A.
        Mutant superoxide dismutase 1-induced IL-1beta accelerates ALS pathogenesis.
        Proc Natl Acad Sci U S A,. 2010; 107: 13046-13050
        • Zhao W.
        • et al.
        TDP-43 activates microglia through NF-κB and NLRP3 inflammasome.
        Exp Neurol. 2015; 273: 24-35
        • Bellezza I.
        • et al.
        Peroxynitrite activates the NLRP3 inflammasome cascade in SOD1(G93A) mouse model of amyotrophic lateral sclerosis.
        Mol Neurobiol. 2018; 55: 2350-2361
        • Johann S.
        • et al.
        NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients.
        Glia. 2015; 63: 2260-2273
        • Evans C.
        • et al.
        Incidence and prevalence of multiple sclerosis in the Americas: a systematic review.
        Neuroepidemiology. 2013; 40: 195-210
        • Wallin M.T.
        • et al.
        The prevalence of MS in the United States: a population-based estimate using health claims data.
        Neurology. 2019; 92: e1029-e1040
        • Haines J.L.
        • et al.
        Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The multiple sclerosis genetics group.
        Hum Mol Genet. 1998; 7: 1229-1234
        • Sintzel M.B.
        • Rametta M.
        • Reder A.T.
        Vitamin D and multiple sclerosis.
        A Comprehensive Rev. Neurol Ther. 2018; 7: 59-85
        • Wingerchuk D.M.
        Smoking: effects on multiple sclerosis susceptibility and disease progression.
        Ther Adv Neurol Disord. 2012; 5: 13-22
        • Gianfrancesco M.A.
        • Barcellos L.F.
        Obesity and multiple sclerosis susceptibility: a review.
        J Neurol Neuromed. 2016; 1: 1-5
        • Levin L.I.
        • et al.
        Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis.
        JAMA. 2005; 293: 2496-2500
        • Bjornevik K.
        • et al.
        Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis.
        Science. 2022; 375: 296-301
        • Frohman E.M.
        • Racke M.K.
        • Raine C.S.
        Multiple sclerosis–the plaque and its pathogenesis.
        N Engl J Med. 2006; 354: 942-955
        • Hemmer B.
        • Kerschensteiner M.
        • Korn T.
        Role of the innate and adaptive immune responses in the course of multiple sclerosis.
        Lancet Neurol. 2015; 14: 406-419
        • van der Valk P.
        • De Groot C.J.
        Staging of multiple sclerosis (MS) lesions: pathology of the time frame of MS.
        Neuropathol Appl Neurobiol. 2000; 26: 2-10
        • Palle P.
        • et al.
        Cytokine signaling in multiple sclerosis and its therapeutic applications.
        Med Sci (Basel). 2017; 5
        • Compeyrot-Lacassagne S.
        • et al.
        Brain multiple sclerosis-like lesions in a patient with Muckle-Wells syndrome.
        Rheumatology (Oxford). 2009; 48: 1618-1619
        • Schuh E.
        • et al.
        Expanding spectrum of neurologic manifestations in patients with NLRP3 low-penetrance mutations.
        Neurol Neuroimmunol Neuroinflamm. 2015; 2: e109
        • Mann C.L.
        • et al.
        Interleukin 1 genotypes in multiple sclerosis and relationship to disease severity.
        J Neuroimmunol. 2002; 129: 197-204
        • Isik N.
        • et al.
        Multiple sclerosis: association with the interleukin-1 gene family polymorphisms in the Turkish population.
        Int J Neurosci. 2013; 123: 711-718
        • Karakas Celik S.
        • et al.
        Interleukin 18 gene polymorphism is a risk factor for multiple sclerosis.
        Mol Biol Rep. 2014; 41: 1653-1658
        • de Jong B.A.
        • et al.
        Production of IL-1beta and IL-1Ra as risk factors for susceptibility and progression of relapse-onset multiple sclerosis.
        J Neuroimmunol. 2002; 126: 172-179
        • Dujmovic I.
        • et al.
        The analysis of IL-1 beta and its naturally occurring inhibitors in multiple sclerosis: The elevation of IL-1 receptor antagonist and IL-1 receptor type II after steroid therapy.
        J Neuroimmunol. 2009; 207: 101-106
        • Hauser S.L.
        • et al.
        Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6.
        Neurology. 1990; 40: 1735-1739
        • Seppi D.
        • et al.
        Cerebrospinal fluid IL-1beta correlates with cortical pathology load in multiple sclerosis at clinical onset.
        J Neuroimmunol. 2014; 270: 56-60
        • Rossi S.
        • et al.
        Cerebrospinal fluid detection of interleukin-1beta in phase of remission predicts disease progression in multiple sclerosis.
        J Neuroinflammation. 2014; 11: 32
        • Malhotra S.
        • et al.
        NLRP3 inflammasome as prognostic factor and therapeutic target in primary progressive multiple sclerosis patients.
        Brain. 2020; 143: 1414-1430
        • Ming X.
        • et al.
        Caspase-1 expression in multiple sclerosis plaques and cultured glial cells.
        J Neurol Sci. 2002; 197: 9-18
        • Wucherpfennig K.W.
        • et al.
        T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions.
        J Exp Med. 1992; 175: 993-1002
        • Huang W.X.
        • Huang P.
        • Hillert J.
        Increased expression of caspase-1 and interleukin-18 in peripheral blood mononuclear cells in patients with multiple sclerosis.
        Mult Scler. 2004; 10: 482-487
        • Barclay W.
        • Shinohara M.L.
        Inflammasome activation in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE).
        Brain Pathol. 2017; 27: 213-219
        • Shaw P.J.
        • et al.
        Cutting edge: critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis.
        J Immunol. 2010; 184: 4610-4614
        • Jha S.
        • et al.
        The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18.
        J Neurosci. 2010; 30: 15811-15820
        • Gris D.
        • et al.
        NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses.
        J Immunol. 2010; 185: 974-981
        • Li S.
        • et al.
        Gasdermin D in peripheral myeloid cells drives neuroinflammation in experimental autoimmune encephalomyelitis.
        J Exp Med. 2019; 216: 2562-2581
        • Inoue M.
        • et al.
        Interferon-beta therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome.
        Sci Signal. 2012; 5: ra38
        • Guarda G.
        • et al.
        Type I interferon inhibits interleukin-1 production and inflammasome activation.
        Immunity. 2011; 34: 213-223
        • Inoue M.
        • et al.
        An interferon-beta-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage.
        Nat Neurosci. 2016; 19: 1599-1609
        • Coll R.C.
        • et al.
        A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases.
        Nat Med. 2015; 21: 248-255
        • Khan N.
        • et al.
        Pharmacological inhibition of the NLRP3 inflammasome as a potential target for multiple sclerosis induced central neuropathic pain.
        Inflammopharmacology. 2018; 26: 77-86
        • Hou B.
        • et al.
        Inhibition of the NLRP3-inflammasome prevents cognitive deficits in experimental autoimmune encephalomyelitis mice via the alteration of astrocyte phenotype.
        Cell Death Dis. 2020; 11: 377
        • Xu L.
        • et al.
        Rapamycin combined with MCC950 to treat multiple sclerosis in experimental autoimmune encephalomyelitis.
        J Cell Biochem. 2019; 120: 5160-5168
        • Guo C.
        • et al.
        Development and Characterization of a Hydroxyl-Sulfonamide Analogue, 5-Chloro-N-[2-(4-hydroxysulfamoyl-phenyl)-ethyl]-2-methoxy-benzamide, as a Novel NLRP3 Inflammasome Inhibitor for Potential Treatment of Multiple Sclerosis.
        ACS Chem Neurosci. 2017; 8: 2194-2201
        • Sanchez-Fernandez A.
        • et al.
        OLT1177 (Dapansutrile), a selective NLRP3 inflammasome inhibitor, ameliorates experimental autoimmune encephalomyelitis pathogenesis.
        Front Immunol. 2019; 10: 2578
        • Maturana C.J.
        • Aguirre A.
        • Saez J.C.
        High glucocorticoid levels during gestation activate the inflammasome in hippocampal oligodendrocytes of the offspring.
        Dev Neurobiol. 2017; 77: 625-642
        • Zhang X.
        • et al.
        Oligodendroglial glycolytic stress triggers inflammasome activation and neuropathology in Alzheimer's disease.
        Sci Adv. 2020; 6: eabb8680
        • Hoglund R.A.
        • Maghazachi A.A.
        Multiple sclerosis and the role of immune cells.
        World J Exp Med. 2014; 4: 27-37
        • Inoue M.
        • et al.
        NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis.
        Proc Natl Acad Sci U S A,. 2012; 109: 10480-10485
        • Galluzzi L.
        • et al.
        Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
        Cell Death Differ. 2018; 25: 486-541
        • Shi J.
        • Gao W.
        • Shao F.
        Pyroptosis: Gasdermin-mediated programmed necrotic cell death.
        Trends Biochem Sci. 2017; 42: 245-254
        • He W.T.
        • et al.
        Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion.
        Cell Res. 2015; 25: 1285-1298
        • Kayagaki N.
        • et al.
        Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling.
        Nature. 2015; 526: 666-671
        • Shi J.
        • et al.
        Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death.
        Nature. 2015; 526: 660-665
        • Sharma D.
        • Kanneganti T.D.
        The cell biology of inflammasomes :.
        Mech inflammasome activ regul. 2016; 213: 617-629
        • Kayagaki N.
        • et al.
        Non-canonical inflammasome activation targets caspase-11.
        Nature. 2011; 479: 117-121
        • Huang X.
        • et al.
        Caspase-11, a specific sensor for intracellular lipopolysaccharide recognition, mediates the non-canonical inflammatory pathway of pyroptosis.
        Cell Biosci. 2019; 9: 31
        • Aglietti R.A.
        • et al.
        GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes.
        Proc Natl Acad Sci U S A,. 2016; 113: 7858-7863
        • Ding J.
        • et al.
        Pore-forming activity and structural autoinhibition of the gasdermin family.
        Nature. 2016; 535: 111-116
        • Liu X.
        • et al.
        Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores.
        Nature. 2016; 535: 153-158
        • Sborgi L.
        • et al.
        GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death.
        EMBO J. 2016; 35: 1766-1778
        • Mulvihill E.
        • et al.
        Mechanism of membrane pore formation by human gasdermin-D.
        EMBO J. 2022; 10https://doi.org/10.1038/s41467-021-27692-9
        • Ruan J.
        • et al.
        Cryo-EM structure of the gasdermin A3 membrane pore.
        Nature. 2018; 557: 62-67
        • Evavold C.L.
        • et al.
        The pore-forming protein Gasdermin D regulates Interleukin-1 secretion from living macrophages.
        Immunity. 2018; 48 (e6): 35-44
        • Heilig R.
        • et al.
        The Gasdermin-D pore acts as a conduit for IL-1beta secretion in mice.
        Eur J Immunol. 2018; 48: 584-592
        • de Vasconcelos N.M.
        • et al.
        Single-cell analysis of pyroptosis dynamics reveals conserved GSDMD-mediated subcellular events that precede plasma membrane rupture.
        Cell Death Differ. 2019; 26: 146-161
        • Mangan D.F.
        • Welch G.R.
        • Wahl S.M.
        Lipopolysaccharide, tumor necrosis factor-alpha, and IL-1 beta prevent programmed cell death (apoptosis) in human peripheral blood monocytes.
        J Immunol. 1991; 146: 1541-1546
        • Ozawa T.
        • et al.
        Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma.
        Cancer Cell. 2014; 26: 288-300
        • Cooper S.T.
        • McNeil P.L.
        Membrane repair: mechanisms and pathophysiology.
        Physiol Rev. 2015; 95: 1205-1240
        • Ruhl S.
        • et al.
        ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation.
        Science. 2018; 362: 956-960
        • Mitra S.
        • Sarkar A.
        Microparticulate P2×7 and GSDM-D mediated regulation of functional IL-1beta release.
        Purinergic Signal. 2019; 15: 119-123
        • Rubartelli A.
        • et al.
        A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence.
        EMBO J. 1990; 9: 1503-1510
        • Andrei C.
        • et al.
        The secretory route of the leaderless protein interleukin 1beta involves exocytosis of endolysosome-related vesicles.
        Mol Biol Cell. 1999; 10: 1463-1475
        • MacKenzie A.
        • et al.
        Rapid secretion of interleukin-1beta by microvesicle shedding.
        Immunity. 2001; 15: 825-835
        • Baroja-Mazo A.
        • et al.
        The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.
        Nature Immunol. 2014; 15 (VN - r): 738-748
        • Valimaki E.
        • et al.
        Calpain activity is essential for ATP-driven unconventional vesicle-mediated protein secretion and inflammasome activation in human macrophages.
        J Immunol. 2016; 197: 3315-3325
        • Zhang Y.
        • et al.
        Inflammasome-derived exosomes activate NF-kappaB signaling in macrophages.
        J Proteome Res. 2017; 16: 170-178
        • Sarkar S.
        • et al.
        Manganese activates NLRP3 inflammasome signaling and propagates exosomal release of ASC in microglial cells.
        Sci Signal. 2019; : 12
        • Rui W.
        • et al.
        Systemic inflammasome activation and pyroptosis associate with the progression of amnestic mild cognitive impairment and Alzheimer's disease.
        J Neuroinflammation. 2021; 18: 280
        • Moreno-Garcia L.
        • et al.
        Inflammasome in ALS skeletal muscle: NLRP3 as a potential biomarker.
        Int J Mol Sci. 2021; 22
        • Dinarello C.A.
        Interleukin-1 in the pathogenesis and treatment of inflammatory diseases.
        Blood. 2011; 117: 3720-3732
        • Blum-Degen D.
        • et al.
        Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients.
        Neurosci Lett. 1995; 202: 17-20
        • Mogi M.
        • et al.
        Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients.
        Neurosci Lett. 1994; 180: 147-150
        • Baroja-Mazo A.
        • et al.
        The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.
        Nat Immunol. 2014; 15: 738-748
        • Wan Z.
        • et al.
        NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis.
        Diabetes Metab Syndr Obes. 2019; 12: 1931-1942
        • Ahmad F.
        • et al.
        Evidence of inflammasome activation and formation of monocyte-derived ASC specks in HIV-1 positive patients.
        AIDS. 2018; 32: 299-307
        • Franklin B.S.
        • et al.
        The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation.
        Nat Immunol. 2014; 15: 727-737
        • Basiorka A.A.
        • et al.
        Assessment of ASC specks as a putative biomarker of pyroptosis in myelodysplastic syndromes: an observational cohort study.
        Lancet Haematol. 2018; 5: e393-e402
        • Forouzandeh M.
        • et al.
        The inflammasome signaling proteins ASC and IL-18 as biomarkers of psoriasis.
        Front Pharmacol. 2020; 11: 1238
        • Weaver C.
        • et al.
        Inflammasome proteins as inflammatory biomarkers of age-related macular degeneration.
        Transl Vis Sci Technol. 2020; 9: 27
        • Kerr N.
        • et al.
        Inflammasome proteins as biomarkers of traumatic brain injury.
        PLoS One. 2018; 13e0210128
        • Kerr N.
        • et al.
        Inflammasome proteins in serum and serum-derived extracellular vesicles as biomarkers of stroke.
        Front Mol Neurosci. 2018; 11: 309
        • Keane R.W.
        • Dietrich W.D.
        • de Rivero Vaccari J.P.
        Inflammasome proteins as biomarkers of multiple sclerosis.
        Front Neurol. 2018; 9: 135
        • Scott X.O.
        • et al.
        The inflammasome adaptor protein ASC in mild cognitive impairment and Alzheimer's disease.
        Int J Mol Sci. 2020; 21
        • Feehan K.T.
        • Gilroy D.W.
        Is resolution the end of inflammation?.
        Trends Mol Med. 2019; 25: 198-214
        • Serhan C.N.
        • Savill J.
        Resolution of inflammation: the beginning programs the end.
        Nat Immunol. 2005; 6: 1191-1197
        • Fullerton J.N.
        • Gilroy D.W.
        Resolution of inflammation: a new therapeutic frontier.
        Nat Rev Drug Discov. 2016; 15: 551-567
        • Lawrence T.
        • et al.
        IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammation.
        Nature. 2005; 434: 1138-1143
        • Martin B.N.
        • et al.
        IKKalpha negatively regulates ASC-dependent inflammasome activation.
        Nat Commun. 2014; 5: 4977
        • Guo C.
        • et al.
        Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome.
        Immunity. 2016; 45: 802-816
        • Xu M.
        • et al.
        Acetate attenuates inflammasome activation through GPR43-mediated Ca(2+)-dependent NLRP3 ubiquitination.
        Exp Mol Med. 2019; 51: 1-13
        • Li C.
        • et al.
        Role of resolvins in the inflammatory resolution of neurological diseases.
        Front Pharmacol. 2020; 11: 612
        • Cao L.
        • et al.
        Resolvin D2 suppresses NLRP3 inflammasome by promoting autophagy in macrophages.
        Exp Ther Med. 2021; 22: 1222
        • Lee J.K.
        • et al.
        Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation.
        PLoS One. 2013; 8: e81785
        • Lee J.K.
        • et al.
        Regulator of G-protein signaling-10 negatively regulates NF-kappaB in microglia and neuroprotects dopaminergic neurons in hemiparkinsonian rats.
        J Neurosci. 2011; 31: 11879-11888
        • Perregaux D.G.
        • et al.
        Identification and characterization of a novel class of interleukin-1 post-translational processing inhibitors.
        J Pharmacol Exp Ther. 2001; 299: 187-197
        • Coll R.C.
        • et al.
        MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition.
        Nat Chem Biol. 2019; 15: 556-559
        • Coll R.C.
        • Schroder K.
        • Pelegrín P.
        NLRP3 and pyroptosis blockers for treating inflammatory diseases.
        Trends in Pharmacol Sci. 2022; : 653-668
        • Dempsey C.
        • et al.
        Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-beta and cognitive function in APP/PS1 mice.
        Brain Behav Immun. 2017; 61: 306-316
        • Klück V.
        • et al.
        Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trial.
        Lancet Rheumatol. 2020; 2: e270-e280
        • Lonnemann N.
        • et al.
        The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer's disease.
        Proc Nationl Acad Sci. 117. 2020: 32145-32154
        • Haseeb M.
        • et al.
        Novel small-molecule inhibitor of NLRP3 inflammasome reverses cognitive impairment in an Alzheimer's disease model.
        ACS Chemical Neuroscience. 2022; 13: 818-833
        • Hardin MD
        • Glyburide J.T.
        Treasure Island.
        StatPearls Publishing, StatPearls FL2022 ([Internet])
        • Lamkanfi M.
        • et al.
        Glyburide inhibits the Cryopyrin/Nalp3 inflammasome.
        J Cell Biol. 2009; 187: 61-70
        • Qiu X.
        • et al.
        Inhibition of NLRP3 inflammasome by glibenclamide attenuated dopaminergic neurodegeneration and motor deficits in paraquat and maneb-induced mouse Parkinson's disease model.
        Toxicol Letters. 2021; 349: 1-11
        • Brogan P.A.
        • et al.
        Rapid and sustained long-term efficacy and safety of canakinumab in patients with cryopyrin-associated periodic syndrome ages five years and younger.
        Arthritis Rheumatol. 2019; 71: 1955-1963
        • Kadry H.
        • Noorani B.
        • Cucullo L.
        A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity.
        Fluids and Barriers of the CNS. 2020; 17: 69
        • Braak H.
        • et al.
        Staging of brain pathology related to sporadic Parkinson's disease.
        Neurobiol Aging. 2003; 24: 197-211
        • Amor S.
        • et al.
        Inflammation in neurodegenerative diseases.
        Immunology. 2010; 129: 154-169
        • Trager U.
        • Tabrizi S.J.
        Peripheral inflammation in neurodegeneration.
        J Mol Med (Berl). 2013; 91: 673-681
        • von Bernhardi R.
        • Eugenin-von Bernhardi L.
        • Eugenin J.
        Microglial cell dysregulation in brain aging and neurodegeneration.
        Front Aging Neurosci. 2015; 7: 124
        • Allan S.M.
        • Rothwell N.J.
        Cytokines and acute neurodegeneration.
        Nat Rev Neurosci. 2001; 2: 734-744
        • Martinez E.M.
        • et al.
        Editor's highlight: Nlrp3 is required for inflammatory changes and nigral cell loss resulting from chronic intragastric rotenone exposure in mice.
        Toxicol Sci. 2017; 159: 64-75
        • Singer II
        • et al.
        The interleukin-1 beta-converting enzyme (ICE) is localized on the external cell surface membranes and in the cytoplasmic ground substance of human monocytes by immuno-electron microscopy.
        J Exp Med. 1995; 182: 1447-1459
        • Tan M.S.
        • et al.
        Amyloid-beta induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer's disease.
        Cell Death Dis. 2014; 5: e1382
        • Tan C.C.
        • et al.
        NLRP1 inflammasome is activated in patients with medial temporal lobe epilepsy and contributes to neuronal pyroptosis in amygdala kindling-induced rat model.
        J Neuroinflammation. 2015; 12: 18
        • Fann D.Y.
        • et al.
        Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke.
        Cell Death Dis. 2013; 4: e790
        • Adamczak S.E.
        • et al.
        Pyroptotic neuronal cell death mediated by the AIM2 inflammasome.
        J Cereb Blood Flow Metab. 2014; 34: 621-629
        • Yogarajah T.
        • et al.
        AIM2 Inflammasome-Mediated Pyroptosis in Enterovirus A71-Infected Neuronal Cells Restricts Viral Replication.
        Sci Rep. 2017; 7: 5845
        • Li X.Q.
        • et al.
        Knockdown of the AIM2 molecule attenuates ischemia-reperfusion-induced spinal neuronal pyroptosis by inhibiting AIM2 inflammasome activation and subsequent release of cleaved caspase-1 and IL-1beta.
        Neuropharmacology. 2019; 160107661
        • Barclay W.E.
        • et al.
        The AIM2 inflammasome is activated in astrocytes during the late phase of EAE.
        JCI Insight. 2022; 7
        • Ma C.
        • et al.
        AIM2 controls microglial inflammation to prevent experimental autoimmune encephalomyelitis.
        J Exp Med. 2021; 218: e20201796
        • Heneka M.T.
        • McManus R.M.
        • Latz E.
        Inflammasome signalling in brain function and neurodegenerative disease.
        Nat Rev Neurosci. 2018; 19: 610-621
        • Voet S.
        • et al.
        Inflammasomes in neuroinflammatory and neurodegenerative diseases.
        EMBO Mol Med. 2022; 7: e155563